1. Field of the Invention
The present invention generally relates to water soluble trans-Pt (II) complexes, their synthesis routes, and their methods of use as anti-cancer agents.
2. Background Description
The use of cisplatin, cis-[PtCl.sub.2 (NH.sub.3).sub.2 ], and carboplatin, [Pt(CBDCA)(NH.sub.3).sub.2 ] (CBDCA=1,1-cyclobutanedicarboxylate), in the treatment of certain cancers is well-established. Nevertheless, there is a continued interest in the design of structurally novel platinum compounds that show antitumor activity complementary to that of the clinical drugs. The fact that transplatin, trans-[PtCl.sub.2 (NH.sub.3).sub.2 ], ##STR1## was found to be therapeutically inactive, has been considered a paradigm for the structure-activity relationships (SAR) of platinum(II) antitumor compounds; trans-Pt compounds have been dismissed as ineffective in vivo agents.
However, the presence of a planar ligand such as pyridine or quinoline, e.g., in trans-[PtCl.sub.2 (NH.sub.3)(quinoline)], ##STR2## dramatically enhances the in vitro cytotoxicity of the trans geometry. The cytotoxic activity of such "nonclassical" trans-platinum complexes has been discussed in terms of both an overall altered affinity toward biologically relevant (N and S) nucleophiles and unique DNA binding modes.
The above "nonclassical" trans-platinum species has, however, been found to have limited bioavailability and, consequently, low in vivo activity. One possible explanation is lack of solubility. It would be clearly desirable to design a trans-platinum species that retains the property of cytotoxicity and yet is water-soluble, thereby enhancing its bioavailability and potential in vivo usefulness for the treatment of tumors.